Leading experimental biologists now realize that conventional investigations and data collection, however fundamental to scientific progress, are no longer sufficient for breakthrough advancements in biomedicine. The missing piece is not so much data management, but rather computer modeling that explains physiological function through the spatial organization and interplay of specific signaling molecules, genes, and proteins. The principal impediments to such modeling are insufficient software and idea-ware computational tools that make increasingly sophisticated models easier to create and manipulate -- and alack of trained scientists able to use such tools effectively. The proposed work targets these needs by expanding development of MCell and DReAMM, unique programs for spatially realistic simulations of stochastic cellular microphysiology. DReAMM is used to pre and post-process MCell models interactively, including powerful 3-D rendering and animation, and MCellitself uses Monte Carlo algorithms to simulate reaction/diffusion systems such as biochemical signaling and reaction networks. Specific aims are major advances in MCell and DReAMM's: (1) Range of application --to include optimized and generalized spatio temporal interactions between moving molecules and molecular complexes, as well as hybrid finite element/Monte Carlo algorithms; (2) Scalability- run-time, algorithm, and user interface extensions to encompass large-scale models with thousands of separate objects (e.g., cells, organelles); (3) Ease of use m numerous critical graphical user interface features; (4) Code validation systematic version checking with an extensive suite of test models; (5) Web-based courses and code distribution for fully independent remote MCell and DReAMM training, and use in teaching and research. In time, given continued development and use of tools like MCell and DReAMM, computational modeling will play a key role in the understanding of human disease, with an impact on the nation's social infrastructure at least as great as that of modern weather modeling and prediction.